The major cell types of the anterior pituitary gland are distinguished by the hormones they produce. Dr. Camper proposes to identify the cis elements and trans factors important for expression of the earliest pituitary hormone marker of commitment, a-subunit, to assess the functional role of a- subunit by gene targeting, and to exploit transgenic mice to define the roles of a-subunit expressing cells in pituitary organogenesis. In addition, the a-subunit deficient mice will be used to test the role of pituitary gonadotropins in gonadal tumorigenesis. Dr. Camper has previously established cell-specific, developmentally appropriate, and hormonally regulated expression of a-subunit reporter gene constructs in transgenic mice. Future experiments will define the minimal essential DNA sequences that are critical for cell specificity, providing the basis for identification of the transcription factors important for expression in thyrotropes. Transgene ablation and cell lineage analysis will be used to distinguish the role of the a-subunit expressing cells from the role of the a-subunit protein. A toxin transgene will be expressed in the pituitary primordium, causing cell ablation and revealing the role of a-subunit expressing cells in pituitary differentiation. A novel site-specific recombination-based binary system that permits cell marking without causing cell death will be developed as a complimentary method for lineage analysis. By combining the approaches of transgene ablation, embryonic stem cell technology, and cell-marking, Dr. Camper will attempt to dissect the contributions of individual cells and individual genes in regulating the normal growth and development of this important organ system.